The study shows that the human antimicrobial peptide LL‑37, at low, non‑toxic concentrations, makes gum‑lining cells produce more of the signaling molecule IL‑8, which attracts neutrophils (a type of immune cell) to sites of inflammation in the mouth.

LL-37, the only member of the antimicrobial peptide cathelicidin family in humans, exerts a variety of biological activities, especially immunomodulation through either direct chemotactic activity or up-regulation of several cytokines and chemokines in various cell types. In this study, we aimed to determine the immunoregulatory effect of LL-37 on Th1/Th2 cytokine expression and production in human gingival epithelial cells (HGECs). Cultured HGECs were treated with different concentrations of LL-37 for different numbers of times. The cytotoxicity of LL-37 was determined by an MTT assay. Total RNA was isolated for RT-PCR and real-time PCR analyses of cytokine expression. Cell-free culture supernatants were assayed for Th1/Th2 cytokine levels by a cytokine bead array. Out of eleven Th1/Th2 cytokines tested, treatment of HGECs with non-toxic doses of LL-37 (2-6 μM) significantly raised only IL-8 levels in the cell-free culture supernatants, when compared to control untreated cells (P <0.05). Consistent with the elevated IL-8 levels, IL-8 mRNA expression was remarkably and significantly induced by LL-37 treatment (P < 0.05), when compared to the modest mRNA induction of other three cytokines, including IL-1β, IL-6, and TNF-α. The time-course study demonstrated a cumulative IL-8 mRNA induction by LL-37 treatment within a 24-hour interval. These findings indicate that LL-37 favorably induces IL-8 expression and secretion in HGECs, suggesting both direct and indirect involvement of LL-37 in neutrophil recruitment into an inflammatory site within diseased periodontal tissues.